Genetic Variant MUC22:p.Thr80Ile (chr6-31025670-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001395414.1(MUC22):c.239C>T(p.Thr80Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,533,170 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000049 ( 1 hom. )

Consequence

MUC22
NM_001395414.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0270

Publications

0 publications found

Variant links:

Genes affected

MUC22 (HGNC:39755): (mucin 22) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MUC22 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.033866197).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395414.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MUC22	NM_001395414.1	MANE Select	c.239C>T	p.Thr80Ile	missense	Exon 2 of 4	NP_001382343.1	E2RYF6
MUC22	NM_001318484.1		c.248C>T	p.Thr83Ile	missense	Exon 3 of 5	NP_001305413.1	E2RYF6
MUC22	NM_001198815.1		c.239C>T	p.Thr80Ile	missense	Exon 3 of 5	NP_001185744.1	E2RYF6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC22	ENST00000561890.1	TSL:2 MANE Select	c.239C>T	p.Thr80Ile	missense	Exon 2 of 4	ENSP00000455906.1	E2RYF6

Frequencies

GnomAD3 genomes

AF:

0.0000527

AC:

AN:

151844

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00155

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000856

AC:

AN:

128492

AF XY:

0.0000570

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000492

AC:

AN:

1381326

Hom.:

Cov.:

AF XY:

0.0000499

AC XY:

AN XY:

681548

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31504

American (AMR)

AF:

0.0000281

AC:

AN:

35534

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25070

East Asian (EAS)

AF:

0.00186

AC:

AN:

35574

South Asian (SAS)

AF:

0.0000127

AC:

AN:

79046

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33740

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1077418

Other (OTH)

AF:

0.00

AC:

AN:

57752

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000527

AC:

AN:

151844

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74172

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41324

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00155

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67938

Other (OTH)

AF:

0.00

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000340

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.65

CADD

Benign

8.6

(source)

DANN

Benign

0.44

DEOGEN2

Benign

0.0027

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.53

M_CAP

Benign

0.022

MetaRNN

Benign

0.034

MutationAssessor

Benign

0.55

PhyloP100

0.027

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.61

Sift

Pathogenic

0.0

Sift4G

Benign

0.18

Vest4

0.17

MVP

0.17

GERP RS

1.1

Varity_R

0.059

gMVP

0.031

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over